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近期 MAO-B 抑制剂结构见解的更新:基于靶点方法的综述。

Recent updates on structural insights of MAO-B inhibitors: a review on target-based approach.

机构信息

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, 142001, India.

出版信息

Mol Divers. 2024 Jun;28(3):1823-1845. doi: 10.1007/s11030-023-10634-6. Epub 2023 Mar 28.

Abstract

Parkinson's disease is a neurodegenerative disorder characterized by slow movement, tremors, and stiffness caused due to loss of dopaminergic neurons caused in the brain's substantia nigra. The concentration of dopamine is decreased in the brain. Parkinson's disease may be happened because of various genetic and environmental factors. Parkinson's disease is related to the irregular expression of the monoamine oxidase (MAO) enzyme, precisely type B, which causes the oxidative deamination of biogenic amines such as dopamine. MAO-B inhibitors, available currently in the market, carry various adverse effects such as dizziness, nausea, vomiting, lightheadedness, fainting, etc. So, there is an urgent need to develop new MAO-B inhibitors with minimum side effects. In this review, we have included recently studied compounds (2018 onwards). Agrawal et al. reported MAO-B inhibitors with IC 0.0051 µM and showed good binding affinity. Enriquez et al. reported a compound with IC 144 nM and bind with some critical amino acid residue Tyr60, Ile198, and Ile199. This article also describes the structure-activity relationship of the compounds and clinical trial studies of related derivatives. These compounds may be used as lead compounds to develop potent compounds as MAO-B inhibitors.

摘要

帕金森病是一种神经退行性疾病,其特征是运动缓慢、震颤和僵硬,这是由于大脑黑质中多巴胺能神经元的丧失引起的。大脑中的多巴胺浓度降低。帕金森病可能是由于各种遗传和环境因素引起的。帕金森病与单胺氧化酶(MAO)酶的异常表达有关,特别是 B 型,它导致生物胺如多巴胺的氧化脱氨。目前市场上可用的 MAO-B 抑制剂具有各种不良反应,如头晕、恶心、呕吐、头晕、昏厥等。因此,迫切需要开发具有最小副作用的新型 MAO-B 抑制剂。在这篇综述中,我们包括了最近研究的化合物(2018 年以后)。Agrawal 等人报道了具有 IC 0.0051µM 的 MAO-B 抑制剂,并显示出良好的结合亲和力。Enriquez 等人报道了一种具有 IC 144nM 的化合物,与一些关键的氨基酸残基 Tyr60、Ile198 和 Ile199 结合。本文还描述了化合物的构效关系和相关衍生物的临床试验研究。这些化合物可以作为先导化合物,开发出作为 MAO-B 抑制剂的有效化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eece/10047469/f52649088563/11030_2023_10634_Fig1_HTML.jpg

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